AIDS chief says he rewrote safety report

Drug's readiness had been doubted

By John Solomon, Associated Press | December 15, 2004

WASHINGTON -- The government's chief of AIDS research rewrote a safety report on a US-funded drug study to change its conclusions and delete negative information. Later, he ordered the research resumed over the objections of his staff, documents show.

Dr. Edmund Tramont, chief of the National Institutes of Health's AIDS Division, took responsibility for both decisions. He cited his four decades of medical experience and argued that Africans in the midst of an AIDS crisis deserved some leniency in meeting US safety standards, according to interviews and documents obtained by the Associated Press.

Tramont's staff, including his top deputy, had urged more scrutiny of the Uganda research site to ensure it overcame record-keeping problems, violations of federal patient safety safeguards, and other issues that forced a 15-month halt to the research into using nevirapine to prevent African babies from getting AIDS from their mothers.

The AP reported Monday that the NIH knew about the problems in early 2002 but did not tell the White House before President Bush launched a plan that summer to spread nevirapine throughout Africa.

Now, officials have new concerns the drug may cause long-term resistance in patients who received it, foreclosing future treatment options.

"I am not convinced that the site is indeed prepared to become active," Dr. Jonathan Fishbein, a specialist the NIH hired to improve the agency's research practices, wrote Tramont in July 2003.

Fishbein contended he should be given time to review Uganda's capabilities and safety monitoring before letting the site reopen, or the NIH would risk being "toothless" in its new efforts to clean up sloppy research practices. He added that professional safety monitors hired by the NIH had reservations about the site.

"I want this restriction lifted ASAP because this site is now the best in Africa run by black Africans, and everyone has worked so hard to get it right as evidenced by the fact that their lab is now certified," Tramont wrote July 8, 2003, in response to Fishbein.

NIH officials acknowledge Tramont rewrote the report and overruled his staff on the reopening, but said he did so because he was more experienced and had an "honest difference of opinion" with his safety specialists. They noted he had no financial interest in nevirapine and that the troubled study began well before he joined NIH in 2001.

Those who raised objections "were part of a large team of which Dr. Tramont was the head, and it is important that the people involved in that team should express their opinion and there should be discussion," said Dr. H. Clifford Lane, the NIH's No. 2 infectious disease specialist and one of Tramont's bosses.

Lane said an internal NIH review concluded Tramont had not engaged in scientific misconduct. Separately, the National Academy of Sciences continues to investigate whether the Uganda research was valid.

NIH believes it helped save hundreds of thousands of African babies by allowing nevirapine to be used in single doses to block the AIDS virus, Lane said. But he acknowledged the research was imperfect, and NIH now believes nevirapine should no longer be a first choice for newborn protection if other options exist because of the newly discovered problems about resistance.

Tramont wrote in 2003 e-mails that he reopened the clinics because he didn't want NIH "perceived as bureaucratic but rather thoughtful and reasonable" and that it was important to encourage Africans' fight against AIDS "especially when the president is about to visit them."

Bush visited the continent a few days after Tramont ordered the clinics reopened.

Tramont's actions, however, drew a blunt reply from his top deputy.

"I think we are cutting off our noses to spite our face here," wrote Jonathan Kagan, the AIDS Division deputy director. "We should not be motivated by political gains, and it's dangerous for you, of all people, to be diminishing the value of our monitors."

Tramont prevailed and the research resumed. A few days later, Tramont sent a note to his staff ordering the end of an 18-month-long debate inside the NIH over whether the science from the Uganda trials was valid and safe. That debate began in early 20002 when two audits divulged widespread problems with the research.

The Uganda trial "has been reviewed, remonitored, debated, and scrutinized. To do any more would be beyond reason. It is time to put it behind us and move on," Tramont wrote in a July 13, 2003, e-mail instructing his staff that future issues about the drug be handled directly by his office.

Five months earlier, Tramont surprised one of his own medical officers who had written a report summarizing safety concerns uncovered during a second review of the Uganda trial.

Dr. Betsy Smith's report, finished in January 2003, said that the Uganda trial suffered from "incomplete or inadequate safety reporting" and that records on patients were "of poor quality and below expected standards of clinical research."

She strongly urged the NIH not to make sweeping conclusions about nevirapine based on the Uganda research. "Safety conclusions from this trial should be very conservative," she wrote.

Behind the scenes, Tramont asked to see Smith's report before it was submitted to medical authorities, including the Food and Drug Administration. "I need to see the primary data -- too much riding on this report," Tramont wrote Jan. 23, 2003.

A few weeks later, the safety report was published and sent to the FDA without Smith's concerns and with a new conclusion.

The study "has demonstrated the safety of single-dose nevirapine for the prevention of maternal to child transmission," Tramont's version concluded. "Although discrepancies were found in the database and some unreported [adverse reactions] were discovered . . . these were not clinically important in determining the safety profile."

In disbelief, Tramont's staff began inquiring how Smith's report got changed. An answer came back from the top.